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Cell Mol Biol Lett. 2019 Feb 22;24:15. doi: 10.1186/s11658-019-0142-4. eCollection 2019.

Honokiol alleviates sepsis-induced acute kidney injury in mice by targeting the miR-218-5p/heme oxygenase-1 signaling pathway.

Author information

1
1Department of of Intensive Care Unit, Tianjin Huanhu Hospital, No. 6 Jizhao Road, Tianjin, 300060 People's Republic of China.
2
2Department of Neurology, Tianjin Huanhu Hospital, Tianjin, 300060 People's Republic of China.
#
Contributed equally

Abstract

Background:

Honokiol is a low-molecular-weight natural product and has been reported to exhibit anti-inflammatory activity.

Objectives:

Our study aimed to investigate the influence of honokiol on sepsis-induced acute kidney injury (AKI) in a mouse model.

Material and methods:

A cecal ligation and puncture (CLP) surgical operation was performed to establish a sepsis-induced acute kidney injury model in mice. Renal histomorphological analysis was performed with periodic acid-Schiff (PAS) staining. The levels of inflammatory markers in serum were measured by ELISA assay. The mRNA and protein levels were assayed by RT-qPCR and western blotting, respectively. Annexin V-FITC/PI staining was used to evaluate glomerular mesangial cell (GMC) apoptosis.

Results:

The results revealed that honokiol significantly increased the survival rate in mice undergoing a CLP operation. Inflammatory cytokines, such as TNF-α, IL-6 and IL-1β, were significantly inhibited in honokiol-treated septic mice compared with the CLP group. In addition, honokiol showed the ability to reverse CLP-induced AKI in septic mice. Furthermore, heme oxygenase-1 (HO-1) expression levels were significantly up-regulated and miR-218-5p was markedly down-regulated in honokiol-treated septic mice as compared to CLP-operated mice. Bioinformatics and experimental measurements showed that HO-1 was a direct target of miR-218-5p. In vitro experiments showed that both honokiol and miR-218-5p inhibitors blocked lipopolysaccharide (LPS)-induced cell growth inhibition and GMC apoptosis by increasing the expression of HO-1.

Conclusions:

Honokiol ameliorated AKI in septic mice and LPS-induced GMC dysfunction, and the underlying mechanism was mediated, at least partially, through the regulation of miR-218-5p/HO-1 signaling.

KEYWORDS:

Acute kidney injury; Heme oxygenase-1; Honokiol; Sepsis

PMID:
30833971
PMCID:
PMC6387556
DOI:
10.1186/s11658-019-0142-4
[Indexed for MEDLINE]
Free PMC Article

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